Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma

Abstract

With the understanding of the complex interaction between the tumour microenvironment and immunotherapy, there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of T cells and immune checkpoint molecules is important for the immune response to cancers. Immune checkpoint molecules include cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), T-cell immunoglobulin mucin protein 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif (TIGIT), glucocorticoid-induced tumour necrosis factor receptor (GITR) and V-domain Ig suppressor of T cell activation (VISTA). Many clinical trials using checkpoint inhibitors, as both monotherapies and combination therapies, have been initiated targeting these immune checkpoint molecules. This review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC, including monotherapies and combination therapies, and provides better treatment options for patients with HNSCC.

Fig. 1

The coinhibitory pathways of head and neck squamous cell carcinoma. During carcinogenesis, T cell activation is inhibited by a number of pathways, which are often activated by the expression of certain ligands on tumour cells or antigen-presenting cells (PD-L1/2, CD80/CD86, galectin 9, LSECtin/FGL1, CD155/GITRL, and VSIG-3) that bind to receptors on T cells (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, GITR, and VISTA) and inhibit the activation and the anti-tumour function of T cells